| | Category | ME | L17 | The Role of Regulatory T Cells in Experimental Autoimmune |
| | Encephalomyelitis |
| | Abstract | Multiple sclerosis (MS) is an autoimmune disease of the central nervous |
| | system affecting about 400,000 people in the US. MS is studied through a |
| | mouse model, experimental autoimmune encephalomyelitis (EAE), which |
| | causes symptoms similar to those of MS in humans, including paralysis. |
| | However, some humans develop MS while others are healthy, without |
| | disease. Likewise, some mouse strains are susceptible to EAE induction |
| | while others are resistant to it. By understanding why certain mouse |
| | strains can resist EAE development, the underlying mechanisms of |
| | disease development can be deciphered. It is thought that one factor |
| | influencing the response to EAE lies in the activities of a population of T |
| | cells known as the regulatory T cells (Treg). It is proposed that resistant |
| | mouse strains have a higher Treg activity and hence lower disease- |
| | causing (effector) activity. SJL.B mice, when immunized with the |
| | neuroantigen MOG, develop EAE. In contrast, no disease is induced when |
| | the mice are immunized with another neuroantigen, MBP. Analysis with of |
| | lymphoid cell populations with a powerful machine called flow cytometry, |
| | it is possible to distinctly separate the disease-causing T cells (effector |
| | cells) from the regulatory T cells (Treg cells). In this project, SJL.B mice |
| | were immunized with the two neuro-antigens, MOG and MBP. T cells |
| | were then sorted by flow cytometry into effector cells expressing high |
| | levels of surface CD4 molecule (CD4hi) and Treg cells expressing CD4 and |
| | CD25 surface molecules (CD4+CD25+). Comparing the frequencies of |
| | Treg cells in MBP-immunized mice (resistant) versus Treg cells in MOG- |
| | immunized mice (susceptible), results showed that EAE resistant mice did |
| | have a higher frequency of Treg cells than did EAE susceptible mice. |
| | These findings establish the significance of Treg cells in the modulation of |
| | EAE and possibly MS. Targeting Treg cells in MS should allow the |
| | development of new therapeutic approaches that can help control the |
| | symptoms of MS. |
| | Bibliography | Shaw, M.K., Kim, C., Ho, K., Lisak, R.P., and Tse, H. Y. A combination of |
| | adoptive transfer |
| | and antigenic challenge induces consistent murine experimental |
| | autoimmune encephalomyelitis |
| | in C57BL/6 mice and other reputed resistant strains. J. Neuroimmunol. |
| | 39:139-149, 1992. |
| | Segal, B. M. and Shevach, E. M. IL-12 unmasks latent autoimmune |
| | disease in resistant |
| | mice. J. Exp. Med. 184:771, 1996. |